Malaria is a disease of epidemic proportions in several parts of the world and is endemic in such areas. In recorded history, malaria leads to more than two million deaths and almost 400 million cases every year in the tropical and subtropical regions of the world (Greenwood et. al Nature (415), 670(2002)). Malaria is a parasitic infection. Of the various forms of malaria that occur, cerebral malaria caused by Plasmodium falciparum, is a significant cause for mortality. Over half of the world population lives in areas where they are susceptible to malarial infection (Sachs et. al, Nature, (415, 686 (2002).
While several drugs are known to be anti-malarial and while governments over the world are taking steps to eliminate the disease by vector control methods, the incidence of malaria has worsened over the past few years. This is primarily due to malarial parasites becoming increasingly resistant to several anti-malarial drugs (Reed et. al, Nature (403), 906(2000)) commercially available like chloroquine (Ringwaid et. al, Bulletin of the world health organization, 77(1), 34, (1999)). Elimination of malaria as a pandemic disease using vector control method such as use of insecticides are rendered more complex due to the parallel spread of resistance in the mosquito vector to currently available insecticides.
Most anti-malarial drugs such as chloroquine, mefloquine, primaquine etc. are product of chemical synthesis. However, over the past few years a significant amount of effort is being made to screen natural resources to obtain new classes of compounds/mixtures which can be used as anti-malarials. Such efforts have led, for example, to the discovery of artemisinin from the Chinese plant Artemisia annua as a potential anti-malarial. The development of resistance in the parasite to existing compounds as well as the vector's resistance to insecticides has resulted in an ongoing and urgent need to identify new classes of anti-malarials and develop them as drugs with varied model of action to overcome the problem of resistance (Tulp et al, Drug discovery today (9) 450, (2004)).
Prior art has focused on the use of plant sources to obtain anti-malarial drugs. For example, the discovery of quinine (Brooking, GB 106430, (1917)) and artemisinin (Klayman, Science (228), 1049 (1985)) hitherto extremely potent anti-malarial drugs, both from plant sources, has lead to the study of plants as anti-malarial agents. The ethanopharmacological approach for the search of new anti-malarial agents from the plant sources has proved to be more predictive. Several research groups are now working to develop new active compounds as an alternative to chloroquine and artether, a derivative of artemisinin. Plants may well prove to be the source of new anti-malarial drugs in view of the success with the two important chemotherapeutic agents, quinine and artemisinin, both of which are derived from plants. Plants in addition to Cichona that have been used against fever and malaria include Dichroa febrifuga, which grows in China. However, being alkaloidal in nature febrigugine and isofibrifugine have been reported to be highly toxic for use in humans (Jiang et. al WO2004000319, (2003)). Recently again in China a naturally derived anti-malarial compound Qinghaoso has been investigated. Recently Ihara et. al disclosed about compounds having anti-malarial activity (U.S. Pat. No. 6,710,074 (2004)) from synthesis. There are several patent documents and published patent applications which disclose different classes of compounds with anti-malarial activity, for example, substitute 1,2,4 trioxane (U.S. Pat. No. 6,737,438 (2004)), flavonoids (WO2004000306 (2003)). Napthylisoquinoline (U.S. Pat. No. 6,627,641 (2003)), indoloquinazoles (U.S. Pat. No. 6,531,487 (2003)), trioxolanes (U.S. Pat. No. 6,486,199 (2002)), betacarboline alkaloids (U.S. Pat. No. 6,143,756 (2000)), vocamine (WO9948501 (1999)), acetyl glucosamine derivatives (DE3220426 (1983) and so on. U.S. Pat. No. 6,710,074, WO2004000319, U.S. Pat. No. 5,362,726, US2003212098, WO2004000306, EP1076057, WO9948501, U.S. Pat. No. 4,290,553, U.S. Pat. No. 6,143,756 and U.S. Pat. No. 6,627,641 disclose compound having anti-Plasmodium falciparum activity with a natural origin, mainly plaints. Natural resources will be the potential sources for future drug development against malaria.